Biopolymers such as proteins or peptides assume three-dimensional structures suitable for their characteristic physiological functions through folding. Proteins are one of the naturally occurring substances that can perform the most various functions (non-patent documents 1-5).
Since the three-dimensional structure of proteins or peptides has to be conserved to maintain their activities in vivo, they are relatively expensive. In addition, they are very difficult to synthesize chemically because they are macromolecules with molecular weights of tens of KDa. Indeed, since natural peptides are easily degraded by various enzymes in the human body and have poor bioavailability, they are difficult to be used as injections or oral drugs and fail to maintain their activities in vivo.
To overcome this problem, methods of substituting the natural amino acids of the natural peptides with D-amino acids, modifying the terminal groups of the peptides, cyclizing the peptides, or the like, have been developed.
For instance, the prion protein (PrP) associated with amyloidosis contains an inhibitory peptide which can inhibit the change in three-dimensional structure. The inhibitory peptide chemically modifies the β-sheet breaker peptide, thereby providing good stability against proteases. A method of converting the inhibitory peptide to two or more inactive fragments has been developed (patent document 1).
Meanwhile, since a polypeptide having multiple directionality which acts on a three-dimensional protein structure having a βαβ motif can form a reproducible three-dimensional peptide structure, it is highly likely to be applied for biochips for diagnosis of diseases, electronic and other new materials including nanotubes, nanostructures necessary for the production of highly integrated semiconductors, and so forth.
However, the development of three-dimensional peptide structures has not been studied actively yet and a new type of peptide that can maintain the structural stability of a substrate recognition site of the peptide has never been reported.